Emphasis has been placed on studies of genetic and environmental risk factors for diabetes and on vascular complications of diabetes in the Pima Indians. The residents of the study area, currently numbering approximately 5000 people, have participated in a longitudinal population study for the last 20 years, allowing observations of the natural history of diabetes mellitus and its complications. Because members of several generations are examined systematically, the study provides an unusual opportunity to examine genetic and environmental factors in the incidence of diabetes. In adolescents and young adults, the familial transmission of diabetes is consistent with a major effect of an autosomal dominant gene. Maternal diabetes in pregnancy also increases the risk of diabetes at an early age in the offspring, an effect which has no simple genetic explanation but appears to be due to metabolic derangements in utero. Diabetes developing after the age of 45 years, however, does not appear to be related to parental diabetes, suggesting that different factors, which may not be genetic, determine diabetes of late onset in this population. Studies of the relationships of genetic markers with diabetes and with racial heritage help quantify effects of heritage on diabetes risk and may lead to the identification of linked diabetes susceptibility genes. Studies of complications of diabetes showed that nephropathy occurred at least as frequently in this population with type 2 diabetes as in other follow-up studies of type 1 diabetes. The incidence of nephropathy was most strongly related to duration of diabetes, plasma glucose concentrations, and blood pressure. A new and very sensitive immunoassay for albuminuria has been developed and will be used as an early indicator of nephropathy. Medial arterial calcification was a frequent complication of diabetes and predicted subsequent need for lower extremity amputation. Other diseases with increased frequency among diabetic subjects were cataract and periodontitis.